Actinic Keratosis (AK) is a carcinoma in situ of the epidermis, an early stage of squamous cell carcinoma (Guidelines for the Management of Actinic Keratoses, Subcommittee of the European Dermatology Forum, 2004/2005). Actinic keratosis often develops in fair-skinned people, particularly in regions of the earth with high UV irradiation. In the US actinic keratoses are the most common premalignant lesions in humans. The incidence is much higher in the Sun Belt and is directly related to light skin and sun exposure. In a study performed in Great Britain, 15% of all men and 6% of all women were affected (Memon A A, Tomenson J A, Bothwell J, Friedmann P S. Prevalence of solar damage and actinic keratosis in a Merseyside population: Br J Dermatol 2000; 142: 1154-1159). The prevalence in Australia is even higher. In approximately 10% of all patients with actinic keratosis and approximately 30% of patients with actinic keratosis and additional immune suppression, the progression to an invasive squamous cell carcinoma at a later stage occurs. In order to avoid this progression an efficient treatment is required.
The current treatments for actinic keratosis consist basically of operative and physical methods and topical pharmacological therapy options. Possible treatments include cryosurgery (freezing), surgical excision, curettage (scraping) with or without electrosurgery (heat generated by an electric current) and topical (applied to the skin) medications. Lasers, chemical peels, dermabrasion, and photodynamic therapy may also be used. Unfortunately, operative and physical methods frequently cause serious adverse reactions and often have a high rate of relapse. Diclofenac-Hyaluronic-Acid (Solaraze®), 5-Fluorouracil and Imiquimod are currently available as topical pharmacological therapies for early stages of AK. Retinoids which could be administered orally against actinic keratosis are not authorized on the German market due to their very serious adverse reactions. The rate of full recovery when using topical therapies is only about 50%. In addition to this moderate success rate, subclinical manifestations of actinic keratosis (frequently occurring in addition to visible lesions) can trigger relapses. They are not visible and therefore the cream is often not applied to them. A further disadvantage of topical application is the fact that the agents must be administered for long periods of time and after a certain time patient compliance decreases. For example, a cream like Imiquimod has to be administered for up to 16 weeks.
The current treatments for actinic keratosis are therefore unsatisfactory and prior to the present invention, there was no adequate oral treatment for actinic keratosis. This is particularly bad in the treatment of advanced actinic keratosis, for which the topical treatments seem to be even less effective